This invention concerns triazolyloligosaccharides, compounds having more than one oligosaccharide wherein the bonding between the oligosaccharide groups is a triazole group. Further disclosed is a process for the preparation of these triazolyloligosaccharides, the use of the compounds as potential enzyme inhibitors, and acetylenic intermediate compounds.
Host cell surface oligosaccharides serve as receptor ligands for protein molecules such as enzymes, antibodies and lectins, and they initiate many critical biological reactions. Unfortunately, these receptor ligands also initiate many harmful biological reactions by providing attachment sites for viruses, toxins, bacteria, etc.
Normally in an oligosaccharide, the constituent monosaccharide groups are linked by ether oxygen linkages. This ether oxygen linkage is difficult to construct chemically. Linking methods are specific for each sugar employed. The ether oxygen linking group is susceptible to hydrolysis by glycosyl hydrolases and non-enzymatic chemical hydrolysis. This ease of hydrolysis makes it difficult to use carbohydrate structures as pharmaceuticals. Further, there are no known methods of automated syntheses for complex oxygen ether linked carbohydrates.
The present invention provides saccharide compounds wherein the linkage is less susceptible to hydrolysis and methods for their preparation.
This invention provides a compound having the structure I, 
wherein each R, independently, is selected from the group consisting of hydrogen, hydroxy, alkoxy having up to 8 carbon atoms, acyloxy having up to 8 carbon atoms, acylamino having up to 8 carbon atoms, C1 to C20 hydrocarbyl and substituted hydrocarbyl and amino;
R3 is selected from the group consisting of H, C1 to C20 hydrocarbyl and substituted hydrocarbyl;
m is 0 or 1, and
n and nxe2x80x2 are, independently, 4 or 5.
Also provided are compounds containing three or more rings characterized in that the linkage between the several rings is a triazolyl group-containing moiety of the structure 
where m and R3 are defined as above.
This invention provides a compound of the structure II, wherein R1 is selected from the group consisting of H, Na, C1-C20 alkyl, wherein R2 is selected from the group consisting of hydroxy, alkoxy having from 1 to 8 carbon atoms, acyloxy having from 1 to 8 carbon atoms, acylamino having 
from 1 to 8 carbon atoms, amino, hydrogen, and guanidino;
wherein R3 is selected from the group consisting of H, C1 to C20 hydrocarbyl, and substituted hydrocarbyl;
wherein R4 is selected from the group consisting of H, acyl having from 1 to 8 carbon atoms, and alkyl having 1 to 20 carbon atoms;
wherein R6 and R6xe2x80x2 are selected from the group consisting of H, OH, C1 to C20 alkoxy, C1 to C20 substituted alkoxy, mono-, di- or oligosaccharide, and alkylideneoxy taken together with R7xe2x80x2 when R7xe2x80x2 is not H, provided that one of R6 and R6xe2x80x2 must be H but R6 and R6xe2x80x2 may not both be H; and
R7 and R7xe2x80x2 are selected from the group consisting of H, acyl having from 1 to 8 carbon atoms, C1 to C20 alkyl, aryl, and alkylidene taken together with an adjacent R6, R6xe2x80x2, R7 or R7xe2x80x2.
Also provided are a compound of the structure III, wherein R3 is selected from the group consisting of H, C1 to C20 hydrocarbyl, and C1 to C20 substituted hydrocarbyl; R8 is selected from the group consisting of H, alkyl having from 1 to 20 carbon atoms, and acyl having from 1 to 8 carbon atoms; 
wherein R6 and R6xe2x80x2 are selected from the group consisting of H, OH, C1 to C20 alkoxy, C1 to C20 substituted alkoxy, mono-, di- or oligosaccharide, and alkylideneoxy taken together with R7xe2x80x2, when R7xe2x80x2 is not H, provided that one of R6 and R6xe2x80x2 must be H but R6 and R6xe2x80x2 may not both be H; and
wherein R7 and R7xe2x80x2 are selected from the group consisting of H, acyl having from 1 to 8 carbon atoms, C1 to C20 alkyl, aryl, and alkylidene taken together with an adjacent R6, R6xe2x80x2, R7 or R7xe2x80x2.
Also disclosed is a process for the preparation of a compound having the structure I, comprising: contacting azides of the structure IA: 
wherein R is selected from the group consisting of hydrogen, hydroxy, alkoxy having up to 8 carbon atoms, acyloxy having up to 8 carbon atoms, acylamino having up to 8 carbon atoms, C1 to C20 hydrocarbyl or substituted hydrocarbyl and amino; n and nxe2x80x2 are, independently, 4 or 5, and m is 0 or 1, with compounds of the structure IB 
wherein R is as described above and R3 is selected from the group consisting of H, C1 to C20 hydrocarbyl and substituted hydrocarbyl.
The present invention also discloses a process for the preparation of a combinatorial library of compounds of the structure I, comprising contacting one or more azides of the structure IA: 
wherein R is selected from the group consisting of hydrogen, hydroxy, alkoxy having up to 8 carbon atoms, acyloxy having up to 8 carbon atoms, acylamino having up to 8 carbon atoms, C1 to C20 hydrocarbyl and substituted hydrocarbyl and amino; n and nxe2x80x2 are, independently, 4 or 5, and m is 0 or 1, with one or more compounds of the structure IB 
wherein R is as described above and R3 is selected from the group consisting of H, C1 to C20 hydrocarbyl and substituted hydrocarbyl.